The Collaborative Depression Study (CDS) has advanced the long-term prospective study of mood disorders. This revised application seeks to extend the prospective annual follow-up of the CDS probands to at least 27 years for all subjects. Renewed funding will permit us to better address the general aim of describing the long-term course of moderate to severe major mood disorders in ways not previously possible and to further investigate the general hypothesis that many individuals with moderate to severe mood disorders will develop a lifelong illness. Since no similar data set exists to collect information of this nature, the next 5 years of continued data collection are essential to gaining a complete perspective of the lifetime course of mood disorders, particularly as many more of our subjects pass the age of 65 when the effects of aging on the course of mood disorders can be better assessed. The specific aims are to provide long-term, prospective, data that will help investigators to study: (1) the patterns and predictors of course of illness and psychosocial outcome in mood disorders; (2) morbidity, mortality and suicide associated with mood disorders; (3) somatic treatment as a mediating variable of outcome in mood disorders; (4) the longitudinal course of syndromal and sub-syndromal affective symptoms in subjects with unipolar and bipolar depressive disorders; and (5) mood disorders and aging.